As a long range goal, we intend to synthesize oligoribonucleotide analogs with a 2'-SH substitution which would be the closest analog of RNA. Such compounds would contribute to our understanding of the factors which determine the pucker of the furanose ring and also the shape of the helix. The novel chemistry necessitates the studies of model compounds. First, we are going to prepare 2'-thio-2'-deoxycytidine 3'-butyl phosphate from the corresponding 2':3'-S,O-phosphate via activation with T2 or according to Michelson. A dinucleotide monophosphate analog would be similarly obtained. These compounds could serve to study the neighboring group effect of SH under acidic and basic conditions. The action of nucleases will also be observed and quantitated. Besides chemical methods, biochemical approaches will also be employed to incorporate 2'-thionucleosides into RNA (or DNA). To this effect, phosphorylation will be attempted with nucleoside kinase and nucleotide kinase. The di- and triphosphates would be included in polymerase reactions. It is hoped that some of these compounds would have interesting biological activities as antimetabolites or antiviral agents (interferon inducer).